Substituted derivatives of 10,11-dihydro-5,10-(iminomethano)-5h-dibenzo, cycloheptenes and preparation thereof

ABSTRACT

There are disclosed herein 11-oxo-, 11-hydroxy-, 11-acyloxy-, 11-alkoxy-, and 11-(substituted amino)- derivatives of 10,11dihydro-5,10-(iminomethano)-5H-dibenzo-(a,d)cycloheptene, and their corresponding 12-alkyl-, 12-alkenyl-, 12-cycloalkyl-, 12aralkyl-, 12-dialkylamino-alkyl-, 13-alkyl-, 13-aralkyl- and 13aryl- derivatives. The compounds are useful central nervous system depressants and methods for their preparation and use are given.

United States Patent 91 Dobson et al.

[ SUBSTITUTED DERIVATIVES OF 10,11-D1HYDRO-5,10- (IMINOMETHANO)-5H-DIBENZO, CYCLOHEPTENES AND PREPARATION THEREOF [75] Inventors: Thomas A. Dobson, Dollard-des-Ormeaux, Montreal, Quebec; Martin A. Davis, Montreal, Quebec, Canada [73] Assignee: Ayerst, McKenna and Harrison Limited, Ville St. Laurent, Quebec,

Canada [*1 Notice: The portion of the term of this patent subsequent to Aug. 3, 1988, has been disclaimed.

[22] Filed: July 23, 1970 [21] Appl. No.: 57,792

[52] US. Cl ..260/286 R, 260/239.3, 260/247, 260/247.7 F, 260/268 PC, 260/287 R,

260/288 R, 260/289 R, 260/348 C, 260/468 C, 260/557 B, 260/570.8 TC, 260/586 R,

[ 1 *Feb. 13, 1973 Primary ExaminerDonald G. Daus Attorney-Andrew Kaflto, Dwight J. Potter and Joseph Martin Weigman 5 7 ABSTRACT There are disclosed herein 1l-oxo-, ll-hydroxy-, llacyloxy-, 1l-alkoxy-, and ll-(substituted amino)- derivatives of 10,1 l-dihydro-S ,10-(iminomethano)- SH-dibenzo-[a,d]cycloheptene, and their corresponding l2-alkyl-, 12-alkenyl-, l2-cycloalkyl-, l2-aralkyl-, l2-dialkylamino-a1kyl-, l3-alkyl-, l3-aralkyland 13- arylderivatives. The compounds are useful central nervous system depressants and methods for their preparation and use are given.

21 Claims, N0 Drawings SUBSTITUTED DERIVATIVES OF 10,1 l-DIHYDRO- 5,10-(IMINOMETHANO)-H-DIBENZO, CYCLOIIEPTENES AND PREPARATION THEREOF BACKGROUND OF THE INVENTION The present invention relates to novel heterocyclic compounds, to intermediates used in their preparation and to processes for preparing these compounds I More specifically this invention relates to ll-substituted derivatives of 10,1 1-dihydro-5,10- (iminomethano)-5H-diebenzo[a,d]ccycloheptenes and to their salts with pharmacologically acceptable acids having useful pharmacologic properties. For example the compounds of this invention exhibit central nervous system depressant and anticonvulsant properties. The compounds of this invention are distinguished by being virtually free from causing ataxia, an undesirable side effect in anticonvulsant drugs. In addition, these compounds possess a low order of toxicity.

The combination of attributes stated above renders the heterocyclic compounds of this invention and their salts with pharmacologically acceptable acids useful and desirable as therapeutic agents.

SUMMARY OF THE INVENTION in which R and R together represent a ketonic oxygen or R represents hydrogen and R represents a hydroxyl, an esterified hydroxyl in which the ester forming group is an aliphatic acid containing from two to four carbon atoms, a lower alkoxy, a dimethylamino, a diethylamino, a pyrrolidino, a piperidino or a morpholino radical; R represents hydrogen, or one of the following organic radicals; a lower alkyl, a lower alkenyl, for example, an allyl, cycloalkylalkyl containing four to seven carbon atoms, for example, a cyclopropylmethyl, a lower aralkyl, for example, a benzyl, phenethyl or trimethoxybenzyl, a dialkylaminoalkyl containing four to nine carbon atoms, for example, dimethylaminoethyl, diethylaminoethyl, dimethylaminopropyl or diisopropylaminopropyl radical, or a heterocyclicalkyl containing from six to twelve carbon atoms and from 1 2 hetero atoms, for example, the pyrrolidinoethyl, piperidinoethyl, 4-methy1- piperazinoethyl, 4'-'phenyl-piperazinoethyl or morpholinoethyl radical; and R represents hydrogen, lower alkyl, a lower aralkyl, for example, the benzyl or phenethyl radical, or a monocyclic aryl containing six to eight carbon atoms, for example, the phenyl radical.

DETAILED DESCRIPTION OF THE INVENTION The heterocyclic compounds of this invention form addition salts with pharmaceutically acceptable acids. Such acid addition salts are included within the scope ofthis invention.

The acid addition salts are prepared by reacting the base form of the compound of formula I with either one equivalent or preferably an excess of the appropriate acid in an organic solvent, such as ether or an ethanolether mixture. These salts, when administered to mammals, possess the same pharmacologic activities as the corresponding bases. For many purposes it is preferable to administer the salts rather than the base compound. Among the acid addition salts suitable for this purpose are salts such as the sulfate, phosphate, oxalate, tartrate, maleate, citrate, and hydrochloride. Both the base compounds and the above acid addition salts have the distinct advantage of possessing a relatively low order of toxicity.

The useful central nervous system depressant activity and the anticonvulsant activity of the heterocyclic compounds of formula I and their acid addition salts with pharmaceutically acceptable acids may be demonstrated in standard pharmacologic tests, such as, for example, the tests described by RA. Turner in Screening Methods in Pharmacology," Academic Press, New York and London, 1965, pp. 69-99 and 164-172, respectively.

When the heterocyclic compounds of this invention are used as central nervous system depressants or anticonvulsant agents in warm-blooded mammals, e.g. rats and mice, alone or in combination with pharmacologically acceptable carriers, the proportion of which is determined by the solubility and chemical nature of the compound, chosen route of administration and standard biological practice. For example, they may be administered orally in solid form containing such excipients as starch, milk sugar, certain types of clay and so forth. They may also be administered orally in the form of solutions or they may be injected parenterally. For parenteral administration they may be used in the form of a sterile solution containing other solutes, for example, enough saline or glucose to make the solution isotonic.

The dosage of the presenttherapeutic agents will vary with the form of administration and the particular compound chosen. Furthermore, it will vary with the particular host under treatment. Generally, treatment is initiated with small dosages substantially less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached. In general, the compounds of this invention are most desirably administered at a concentration level that will generally afford effective results without causing any harmful or deleterious side effects and preferably at a level that is in a range of from about 1.0 mg to about 200 mg per kilo per day, although as aforementioned variations will occur. However, a dosage level that is in the range of from about 10 mg to about mg per kilo per day is most desirably employed in order to achieve effective results.

The heterocyclic compounds of this invention may be prepared readily from the key intermediate of formula II:

This key intermediate may be synthesized by one of the following two processes:

in the first process, illustrated by HO. 1, lO-methoxy-Sl-l-dibenzo[a,d]cycloheptene-5-carboxamide (lll), described by M.A. Davis, T.A. Dobson and .l.M. .lordan, Can. J. Chem, 47, 2827 (1969), is used as the starting material Figure 1 V The starting material of formula III on treatment with sodium hypochlorite in methanol gives the carbamate of formula IV. Subsequent treatment of the latter compound with a base, for example, sodium hydroxide, in the presence of water and an inert solvent, for example, dioxane, ethanol or a mixture thereof, affords the key intermediate of formula ll.

in the above process a by-product is obtained in the first step, [ll IV. In addition to the desired carbamate of formula IV, 1 l,l2-dichloro-l0,l l-dihydro-IO- methoxy-S l iminomethano)- 5 H-dibenzo[a,d] cycloheptenl 3-one (V) is also obtained.

The formation of the byproduct of formula V may be suppressed by very slow addition of the reagent, sodium hypochlorite, to the reaction mixture. This byproduct has useful antimicrobial activity and exhibits activity against a number of gram-positive and gramnegative microorganisms, such as, Staphylococcus pyogenes, both penicillin sensitive and penicillin resistant, Sarcina lutea, Streptococcus fecalis, Escherichia coli, Aerobacter aerogenes, Salmonella pullorum, Proteus mirabilis and Proteus vulgaris and has antifungal activity against a number of pathogenic fungi such as, Candida albicans, Microsporum gypseum and Trichaphyton granulosum, in standard tests for antibacterial and antifungal activity, such as those described in Antiseptics, Disinfectants, Fungicides and Sterilization, G.F. Reddish, Ed., 2nd ed., Lea and Febiger, Philadelphia, [957 or by D.C. Grove and W.A. Randall in Assay Methods of Antibiotics, Med. Encycl. Inc. New York 1955.

When this byproduct of formula V is employed as an antibiotic or antifungal agent in warm-blooded animals, e.g. rats, alone or in combination with pharmacologically acceptable carriers, the proportion of which is determined by the solubility and chemical nature of the compound, chosen route of administration and standard biological practice. For example, it may be administered orally in solid form containing such excipients as starch, milk sugar, certain types of clay and so forth. It may also be administered orally in the form of solutions or they may be injected parenterally. For parenteral administration it may be used in the form of a sterile solution containing other solutes, for example, enough saline or glucose to make the solution isotonic.

The dosage of the byproduct of formula V will vary with the form of administration and the particular compound chosen. Furthermore, it will vary with the particular host under treatment. Generally, treatment is initiated with small dosages substantially less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstances is reached. In general, this byproduct is most desirably administered by a concentration level that will generally afford effective results without causing any harmful or deleterious side effects and preferably at a level that is in a range of from about 0.1 mg to about mg per kilo per day, although as aforementioned variations will occur. However, a dosage level that is in the range of from about 0.5 mg to about 50 mg per kilo per day is most desirably employed in order to achieve effective results.

In addition, the agent may be employed topically. For topical application it may be formulated in the form of solutions, creams, or lotions in pharmaceutically acceptable vehicles containing 0.1 5 percent, preferably, 2 percent of the agent and may be administered topically to the infected area of the skin.

The second process for the preparation of the key intermediate of formula ll is illustrated by FIG. 2.

w 9 EEK) in this process the starting material, the epoxyketone of formula Vl described by .l. Rigaudy and L. Nedlec, Bull. Soc. Chim. France, 400 (1960), is reduced by hydrogenation in the presence of a noble metal catalyst, for example, palladium, to give the hydroxy ketone (Vll). This latter compound is oxidized with hexavalent chromium ion, for example, chromic acid in sulfuric acid and water, to yield the diketone(Vlll), which may be converted readily to the enol other UK) on treatment with methanol and an acid catalyst, for example, hydrochloric acid. Subsequent treatment of said enol ether with hydrox- NH: x1.

This alternate intermediate may be prepared by one of the two following processes:

In the first process, illustrated by FIG. 3, the epoxyamide of formula XII,

sea

ONH: NHCOOOH:

XII. XIII- NHCOOCH:

XIV.

NHC 00 OH:

Figure 3 described by TA. Dobson, M.A. Davis, A.M. Hartung and J. Manson, Can. J. Chem., 46, 2843 (1968), is treated with sodium hypochlorite in methanol to give the carbamate (XIII), which when treated with hydrogen in the presence of a catalyst, for example, palladium on charcoal, affords the hydroxy carbamate of formula XIV. Oxidation of the latter compound by hexavalent chromium ion, for example, chromic acid in the presence of sulfuric acid and water, gives the ketocarbamate of formula XV. This ketocarbamate may also be obtained by acid hydrolysis, for example, with -20 percent aqueous hydrochloric acid, of the carbamate of formula IV, described above. The ketocarbamate (XV) may now be converted to the desired alternate intermediate of formula XI by alkaline hydrolysis, for example, by aqueous sodium hydroxide.

As experienced previously in the first process for the preparation of the key intermediate (ll), treatment of the starting material of formula XII of the present process with sodium hypochlorite also results in a byproduct. Thus, in addition to the desired carbamate (XIII), N,N-dichloro-l0,l I-epoxy-IO,I I-dihydro-SH- dibenzo[a,dcyclohepten-5-amine (XVI), is also obtained as a byproduct.

NC]: xvr.

The formation of this byproduct during this reaction may be suppressed by slow addition of the reagent, sodium hypochlorite, to the reaction mixture. This byproduct has the useful antimicrobial activity described above for byproduct V and may be used as a antimicrobial agent in the same manner as byproduct V.

The second process for the preparation of the alternative intermediate of formula XI is illustrated by FIG.

NBC 000 Hz XVII.

Figure 4 In this second process, the carbamate (XIII), described above, is heated with diethylamine, in an inert solvent, for example toluene, to yield the hydroxyamine (XVII). The latter compound, after treatment with an organic peracid in an inert solvent, for example, m-chloroperbenzoic acid in chloroform, yields the corresponding N-oxide of the hydroxyamine (XVII) which loses the elements of diethylamine N-oxide upon treatment with aqueous alkali to give the ketocarbamate of formula XV. Conversion of the latter compound to the desired alternate intermediate(Xl) is then effected in the same manner as described for the preceding process.

The essential ring system of the heterocyclic compounds of this invention may be formed by allowing either the key intermediate (II) or the alternate intermediate (Xl) to react with an appropriate aldehyde, R-CHO in which R is as defined above, according to the conditions ofthe Mannich reaction, see F.F. Blicke, Organic Reactions, I, 303 (I942). In this manner the lI-keto compounds of formula I in which R and R together represent a ketonic oxygen, R represents hydrogen and R is as defined above, are obtained by an intramolecular Mannich reaction.

More specifically the above lI-keto compounds are readily obtained by allowing said intermediate (II) or (XI) to react with at least one equivalent, preferably three to ten equivalents of the appropriate aldehyde in an inert solvent, for example, 1,2-dimethoxyethane, ethanol or acetic acid, at temperatures ranging from room temperature to the boiling point of the reaction mixture for a period of 20 minutes to 18 hours.

The l l-keto compounds of formula I in which R and R together represent a ketonic oxygen, R is defined as above and R represents a lower alkyl, a lower alkenyl, a lower cycloalkyl, a lower aralkyl, a dialkylaminoethyl containing four to nine carbon atoms or a heterocycli calkyl containing 6 to 12 carbon atoms and from one to two hetero atoms, are prepared by treating the corresponding ll-keto compounds of formula I in which R is hydrogen, described above, with an appropriate organic halide of formula RX in which R is one of the organic radicals as defined in the first instance for R and X is a chlorine, bromine or iodine atom, in the presence of a basic condensing agent, for example, sodium hydride, in an inert solvent for example, benzene.

The l l-keto compounds of formula i in which R and R represent together a ketonic oxygen and R and R 'are as defined in the first instance may be reduced to their corresponding ll-hydroxy derivatives, compounds of formula I in which R represents hydrogen, R represents a hydroxyl and R and R are as defined in the first instance, by a variety of known methods for converting a carbonyl group to a carbinol group; for example, see O.H. Wheeler in The Chemistry of the Carbonyl Group, S. Patai, Ed., lnterscience Publishers, London, 1966, pp. 507-566. Preferred reagents for this reduction are lithium aluminum hydride and sodium borohydride.

The ll-esterified hydroxyl compounds of formula I in which R and R are hydrogen, R is an esterified hydroxyl containing two to four carbon atoms and R is as defined in the first instance, may be prepared by treating the corresponding ll-hydroxy derivatives in which R is hydrogen, described above, with an excess of the appropriate aliphatic acid, for example, acetic, propionic or butyric acid in the presence of at least one equivalent of a. mineral acid, for example, 5.0 equivalents of hydrobromic acid.

The l l-esterified hydroxyl compounds of formula I in which R is hydrogen, R is an esterified hydroxyl containing, two to four carbon atoms, R is one of the organic radicals as defined in the first instance, and R is as defined originally, may be prepared by treating the corresponding l l-hydroxy derivatives with the appropriate lower acyl anhydride, for example, acetic anhydride, propionic anhydride or butyric anhydride, in pyridine solution.

The ll-lower alkoxy compounds of formula I in which R is hydrogen, R is a lower alkoxy, R is hydrogen and R is as defined in the first instance may be prepared by treating the corresponding ll-keto compounds of formula I in which R is hydrogen, described above, with a lower aliphatic acyl halide, e.g. acetyl chloride, in pyridine solution to afford the corresponding ll-keto-N-acyl derivatives which on subsequent treatment with sodium borohydride in an inert solvent, for example, tetrahydrofuran, afford the corresponding l l-hydroxy-N-acetyl derivatives of formula I. The latter compounds may then be treated with a lower alkyl chloride, bromide or iodide in the present of a basic condensing agent, for example, sodium hydride in an inert solvent, for example, dimethylformamide to give the corresponding 1 l-lower alkoxy-N- acyl derivatives. The latter compounds yields the desired ll-lower alkoxy compounds of formula I in which R and R are both hydrogen, R is lower alkoxy and R is as defined originally on hydrolysis with an aqueous solution of excess alkali metal hydroxide, for example, sodium or potassium hydroxide, preferably with an inert cosolvent, for example, ethanol.

The t l-lower alkoxy compounds of formula I in which R is hydrogen, R is a lower alkoxy, R is one of the organic radicals as defined in the first instance and R is as defined in the first instance may be prepared by treatment of the l l-lower alkoxy compound of formula I in which R and R are both hydrogen, R is lower alkoxy and R is as defined in the first instance, described above, with an appropriate organic halide of formula RX in which R is one of the organic radicals as defined in the first instance for R and X is a chlorine, bromine or iodine atom, in the presence of a basic condensing agent, for example, sodium hydride, in an inert solvent, for example, benzene.

The heterocyclic compounds of formula I in which R and R are both hydrogen, R is a substituted amino, for example, dimethylamino, diethylamino, pyrrolidino, piperidino or morpholino and R is as defined in the first instance are prepared in the following manner. Thus, the ll-hydroxy-N-acetyl derivatives of formula I, described above, are subjected to a displacement reaction in which the l l-hydroxyl is replaced by a bromine. This displacement reaction may be accomplished by treating said ll-hydroxy-N-acetyl derivatives with phosphorus tribromide in an inert solvent, for example, benzene at a temperature ranging from 0-80 "C for 5a to 24 hours. Alternatively, the replacement may be done in a two step sequence in which the corresponding o-tosyl derivative of said i l-hydroxy-N- acetyl derivatives are prepared with p-toluenesulfonyl chloride in pyridine solution, followed by treatment of the resulting o-tosyl derivative with an excess of lithium bromide in acetone solution at temperatures ranging from 0 to 50C for periods of time of l to 6 hours. The l l-bromo-N-acetyl derivatives thus obtained by the displacement reaction may now be heated at an elevated temperature, for example, l20C, for one to five hours with an excess of the appropriate secondary amine, dimethyl-amine, diethylamino, pyrrolidine, piperidine or morpholino. Subsequent hydrolysis under alkaline conditions, as described above, yields the compounds of formula I in which R and R are both hydrogen, R is dimethylamino, diethylamino, pyrrolidino, piperidino or morpholino and R is as defined in the first instance.

The heterocyclic compounds of formula I in which R is hydrogen, R is substituted amino as defined above, R is an organic radical as defined above and R i is as defined in the first instance may be prepared in the following manner. Thus, the corresponding 1 l-hydroxy compounds of formula I, described above, are subjected to the preceding displacement reaction to yield the corresponding l l-bromo derivatives. Subsequent treatment of the latter compounds with the appropriate secondary amine as described above, yields the desired heterocyclic compounds of formula I.

XVIII.

XIX.

Flgureb According to the processof FlG. 5, a rnixt ure TH) bromo-SH-dibenzo[a,d]cyclohepten--one (XVIII) described, by W. Treibs and 11.]. Klinkhammer, Chem. Bev., 84, 671 (1951), and a molar excess of cuprous cyanide optionally diluted with quinoline is heated at a temperature within the range of 150-220C for a period of 0.5 to 3 hours. The reaction mixture is partitioned between a suitable water immiscible solvent such as, for example, chloroform or methylene chloride and an aqueous mineral acid. Evaporation of the organic phase leaves lO-cyano-5I-I-dibenzo[a,d]cyclohe pten-S-one (XIX).

In its turn a mixture of the latter compound and a molar excess of sodium or potassium or lithium borohydride and a solvent, for example, a lower alkanol containing from one to four carbon atoms or dimethyl sulfoxide is kept at a temperature within the range of 20-l00C for a period of up to two days. The

excess hydride is destroyed with a dilute mineral acid and 10,1 l-dihydro-S,l0-(epoxymethano)-5I-ldibenzo[a,dcyclohepten-l3-one (XX) is thereupon isolated in a conventional manner.

In its turn, the latter compound is treated with either a molar excess of aqueous ammonium hydroxide or a molar excess of an aqueous solution or suspension of a primary amine of formula R NI-I wherein R is an organic group as defined in the first instance, at a temperature within the range l-230C for a period of between 6 to 24 hours to give, after removal of the excess amine, a compound of formula XXI wherein R is as defined in the first instance.

Optionally, the compounds of formula XXI wherein R is limited to represent hydrogen may be alkylated with an organic halide of formula R"X wherein R is an organic group as defined in the first instance and X represents a chlorine, bromine or iodine atom to give a compound of formula XXI wherein R is an organic group as defined in the first instance. This alkylation is carried out in an inert solvent such as, for example, dioxane or benzene in the presence of a basic condensing agent, for example, sodium hydride.

v The compounds of formula XXI in which R is an organic radical as defined in the first instance are used to prepare certain compounds of formula I by the processes illustrated by FIG. 6.

XXI

REN- =0 XXII.

XXIV.

Figure 6 Accordingly the proces ses illustrated by FIG. 6 are employed as follows:

Treatment of the compounds of formula XXI, in which R is an organic radical as defined in the first instance, excluding alkenyl with a N-chloroor N-bromoamide or -imide, e.g. Nbromosuccinimide in an inert solvent, for example, carbon tetrachloride, yields the 1 l-bromo compounds of formula XXII. Preferably, this reaction is performed in the presence of a catalytic amount of an organic peroxide, preferably, benzoyl peroxide at temperatures ranging from 10 to 50C for l to 5 hours. The l I-bromo compounds thus obtained may be employed in the first instance to prepare the alkoxy compounds of formula XXIII in which R represents methyl, ethyl or propyl. When employed in this manner the ll-bromo compounds are allowed to react with a lower alkoxide ion. Suitable conditions for this reaction include mixing a solution of the 1 l-bromo compounds in lower alkanol, preferably methanol, with a solution of an alkali metal lower alkoxide in a lower alkanol, preferably sodium methoxide in methanol, and allowing the mixture to react at temperatures from 20 to the boiling point of the mixture from 6 hours to 2 or 3 days. The ll-alkoxy compound of formula XXIII in which R is an organic radical as defined above excluding alkenyl and R represents methyl, ethyl or propyl, thus obtained, are reduced readily by suitable reducing agents, preferably lithium aluminum hydride in an inert solvent, for example, tetrahydrofuran to yield those compounds of formula I in which R' and R are both hydrogen, R is lower alkoxy and R is an organic radical as defined in the first instance excluding alkenyl.

In the second instance the ll-bromo compounds of formula XXIII in which R is an organic radical as defined in the first instance excluding alkenyl, described above, may be used to prepare the corresponding ll-hydroxy derivatives, described above.

when employed in this manner, the l l-bromo compounds are allowed to react with an alkali metal hydroxide, preferably potassium hydroxide, in an inert,

water-miscible solvent, for example, dioxane and water. Suitable conditions for this reaction include a temperature range of from room temperature to the boiling point of the mixture and reaction times of from 1 to 24 hours. The ,l l-hydroxyamides of formula XXIII in which R is an organic radical as defined above and R is a hydrogen, thus obtained, are readily reduced by a suitable reducingagent, preferably lithium aluminum hydride, in an inert solvent, for example, tetrahydrofuranto yield those compounds of formula 1 in which R and R are both hydrogen, R is a hydroxy and R is an organic radical as defined in the first instance excluding alkenyl. t

" 1n the third instance the ll-bromo compounds of formula XXll in which R is an organic radical as defined in the first instance excluding alkenyl, described above, are allowed to react with an appropriatesecondary amine to afford the compounds of formula XXIV -in which NRR represents dimethylamino, diethylamino, pyrrolidino, piperidino or morpholino. This reaction may be accomplished conveniently by heating the l l-bromo compounds in a solution of the appropriate secondary amine attemperatures ranging from 60C to 120C from one to five hours. Subsequent reduction of the resulting compounds of' formula XXIV with a suitable reducing agent, preferably lithium aluminum hydride, in'an inert solvent, for example, tetrahydrofuran, yields the heterocyclic' compounds of this invention of formula 1 in which R and R both are hydrogen, R is dimethylamino, diethylamino, pyrrolidino, piperidino or morpholino and R is an organic radical as defined in the first instancelexcluding alkenyl.

4 he'follo'wing Examples will illustratefurtherthis in- .vention.

EXAMPLE 1 Methoxy-51-1-Dibenzo[a,d]Cycloheptene-5- Carbamic Acid Methyl Ester (1V) 5 percent Sodium hypochlorite solution (45 ml) is added at room temperature, over 2 hours to a solution of 10-methoxy-5H-dibenzo[a,d]cyc1oheptene-5-carb'oxamide (111), (5.0 g, 0.019mole) in dioxane (80 ml)v and methanol (250 ml). The reaction mixture is then diluted with water and filtered to give the crude title I compound, m.p. l95-198C. Recrystallization from tcwhloroform gave the pure product, m.p. 200'-202C;

vmgf 3440 cm (NH); 1710 cm (carbamate);

,t,,,,, H 288 mu (e -12400); nmr (DMSO), ;1.17' (Ni-[,d); 2.55 (8-1-1, aromatic, m); 3.43 (l-Hat C-1 1 s); 4.67 (1-1-1 arc-5, d);.,6.03 (lo-coughs )i 6.37 comm 1 I EXAMPLE 2 10-Methoxy-SH-Dibenzo[a,d}Cyc1ohepten-5-amine A solution of 10-methoxy-S1-1-dibenzo]a,d]cyclohe ptene-S-carbamic acidmethyl ester (1V, 4.2 g, 0.014 mole), described in Example 1, and sodium hydroxide (5.25 g) in a mixture of water (40 ml), dioxane (75 m1) and ethanol (112 ml) is heated under reflux for 18 hours. The organic solvents are removed under reduced pressure and the product is extracted into chloroform, washed with water and dried. Chromatography over alumina (neutral, activity 11) with benzene gives the title compound, m.p. 101-102C; 9,5 3370, 3,300 cm (N11 h 284 mp. (e 11,510); nmr (CDCl 2.50 (8-H, aromatic, m); 3.63

, 8.15 (Ni-l br. .r); on addition of D 0, 2 exchanged protons (8.15) are observed. EXAMPLE 3 l 1,12-Dichloro-10,1 l-Dihydrd-lO-Methoxy-10,5-

(lminomethano )-51-1-Dibenzo[a,d] Cyclohepten 1 3 one (V) 5 percent Sodium hypochlorite solution (63 ml) is added in one portion to a stirred solution of lp-methoxy-5l-l-dibenzo[a,d]-cycloheptene-S-carboxamide (111,

7.0 g, 0.028 mole) in dioxane (112 m1) and methanol (350 ml). The warm solution is cooled and then stirred at room temperature for 1 hour. Dilution with water and filtration give the crude title compound which is chromatographed on silica gel. Elution with benzene followed by crystallization from chloroform-hexane gives the pure title compound, m.p. 193?-195C;

457); nmr (DMSO)-r 2.50 (8-H, aromatic, m); 3.80 (1-H at'C-5,s); 4.62 (1-1-1 at C-10, s); 6.25 (OCH:,', .5);

EXAMPLE 4 10,1 l-Dihydro- 1O-Hyclroxy-Sl-l-Dibenzo[a,d ]Cyclohepten-5-one (V11) fractions 7 to 15 when 250 ml fractions are taken. This product, which is suitable for. use in the following Examp1e, gives a white solid, mp 87C, A f 268 mp. (e=1'3,300), on trituration with hexane.

EXAMPLE 5 5l-l-Dibenzo[a,d]Cycloheptene-5,10( 1 l1-l)-dione To a solution of 10,1l-dihydro-lO-hydroxy-SH- dibenzo- [a,d]cyclohepten-5-one (V11, 29.5 g, 0.132 mole), prepared as described in Example 4, in acetone 10 percent isopropyl alcohol-benzene). The

(500 ml) is treated dropwise with 30.5 ml of chromic acid sulfuric acid reagent, A. Bower et al., J. Chem. Soc., 2548 (1953), at room temperature. The reaction mixture is then stirred for an additional 30 minutes. The reaction mixture is filtered. Concentration of the filtrate yields the title compound, which on crystallization from acetone-hexane gives a solid, m.p. 1 l7-l 19 C.

EXAMPLE 6 10-Methoxy-5H-Dibenzo[a,dlCyclohepten-5-Ones A solution of H-dibenzo[a,d]cycloheptene-5,10- dione (Vlll, 22.1 g, 0.995 mole), prepared as described in Example 5, in methanolic hydrochloric acid (300 ml) is boiled for 3 hours. On cooling the reaction mixture, the title compound, m.p. 96-97C, is obtained as a solid precipitate.

EXAMPLE 7 l0-Methoxy-5 H-Dibenzo[a,d]Cycl0hepten-5-one Oxime (X) A solution of -methoxy-SH-dibenzo[a,d]cyclohe pten-S-one (1X, 16.5 g, 0.07 mole), prepared as described in Example 6, hydroxylamine hydrochloride (33.0 g), and pyridine (150 ml) is heated on a steam bath for 2 hours. Most of the pyridine is removed by evaporation under reduced pressure. The residue is dissolved in ether and washed well with water. Evaporation of the ether solution yields the title compound, which on recrystallization from methanol gives crystals, m.p. 184-189C.

EXAMPLE 8 lO-Methoxy-Sl-l-Dibenzo[a,d]Cyclohepten-5-amine lO-Methoxy-SH-dibenzo[a,d]cyclohepten-S-one oxime (X, 15.2 g, 0.0605 mole), prepared as described in Example 7, is dissolved in methanol (600 ml) and 2N-sodium hydroxide (400 ml). Raney nickel alloy (22.0 g) is added in one portion. The reaction mixture is stirred for one hour; during the first ten minutes the.

temperature of the reaction mixture rises to 50C. After filtering, the methanol is removed from the reaction mixture by evaporation. The resulting aqueous phase is extracted with benzene. The benzene extract is dried and concentrated. The residue is crystallized from ether-hexane to afford the title compound, identical to the product obtained in Example 2.

EXAMPLE 9 10,1 1-Dihydro-10,l 1-Epoxy-5H-Dibenzo[a,d ]Cycloheptene-5-Carbamic Acid Methyl Ester (X111.)

5 percent Sodium hypochlorite solution (200 ml) is added, at room temperature, over 5 hours to a solution of 10,1 l-dihydro-l0,l l-epoxy-5 H-dibenzo[a,d] cycloheptene-S-carboxamide (X111, 35.0 g, 0.14 mole) in dioxane (30 ml) and methanol (900 ml). The reaction mixture is diluted with a large volume of water. The resulting precipitate is collected and washed with water to give the title compound, m.p. 143146C.

Recrystallization from ethyl acetate -hexane gives the pure product, m.p. l46-l47C; 35, 3,420 cm" (NH); 1,720 cm (carbamate); A 262, 265 my. (6 814), 274 mu (e 619).

EXAMPLE l0 10,1 l-Dihydro-l0-Hydroxy-5H-Dibenzo[a,d ]Cycloheptene-5-Carbamic Acid Methyl Ester (XlV.)

EXAMPLE 1 1 10,1 1-Dihydro-10-Oxo-5H-Dibenzo[a,d ]Cycloheptene-5-Carbamic Acid Methyl Ester (XV) A solution of 10-hydroxy-5-H-dibenzo[a,d]cyclohe ptene-S-carbamic acid methyl ester (XIV, 11.0 g, 0.038 mole), prepared as described in Example 10, in dioxane (120 ml) and acetone (350 ml) is treated dropwise over 15 minutes with 14 ml of chromic acid-sulfuric acid reagent at 5C. The reaction mixture is stirred for 45 minutes during which time it is allowed to come to room temperature and then filtered. The filtrate is concentrated under reduced pressure. The residue is triturated with water and crystallized from benzene to afford the title compound, m.p. 233235 C, h f' 288 mu.

EXAMPLE l2 5-Amino-5,l l-Dihydro-10H-Dibenzo[a,d ]Cyclohepten-l0-one (1X) 10-Oxo-5H-dibenzo[a,d]cycloheptene-S-carbamic acid methyl ester (XV, 2 g. 0.007 mole) prepared as described in Example 11, and sodium hydroxide (2.4 g) are refluxed in a mixture of water (10 ml), dioxane (28 ml) and ethanol (50 ml) for 5 hours. The reaction mixture is evaporated to dryness and the residue is partitioned between chloroform and water. The product from the chloroform phase is crystallized from benzene to give the title compound, m.p. 146147C; 'yg

1,695 (sh), 1,670 cm (ketone); k 292 my. (e 580).

EXAMPLE l3 N,N-Dichloro-10,1 l-Dihydro-l0,1 1-Epoxy-5 H- Dibenzo[a,dc]Cyclohepten-5-amine (XVI) 5 percent Sodium hypochlorite solution ml) is added in one portion to a stirred solution of 10,11- dihydro-10,l 1-epoxy-5H-dibenzo[a,d]cycloheptene-5- carboxamide (XlI, 5.0 g, 0.02 mole) in methanol (200 ml) and the stirring is continued for 1 hour at room temperature. Dilution with water and filtration gives a EXAMPLE 14 10,1 1-Dihydro-l0-Oxo-5H-Dibenzo[a,d JCycIOhe tene-S-Carbamic Acid Methyl Ester (XV) via the intermediate, l-Diethylamino- 10,1 l-Dihydro- H-Dibenzo[a,dlCycloheptene-S-Carbamic Acid Methyl Ester (XVII) A solution of 10,1 l-dihydro-l0,l l-epoxy-S-dibenzo- {a,d]5-carbamic acid methyl ester (X111, 2.8 g, 0.01 mole) in dry toluene (60 ml) and diethylamine (7.2 g, 0.01 mole) is boiled for 74 hours. The reaction mixture is concentrated to dryness under reduced pressure. Starting material is recovered by crystallization of the resulting residue from chloroform. Concentration of the mother liquors affords the title intermediate, y 1,720 cm". This crude intermediate is further characterized as its corresponding hydrochloride by treating a portion thereof with ethereal hydrogen chloride to give the said hydrochloride, which on recrystallization from ethanol has m.p. 245C (dec.).

Treatment of the title intermediate with mchloroperbenzoic acid in chloroform followed by treatment with alkali according to the conditions of N.L. Bauld and Y.S. Rim, .1. Am.Chem. Soc., 89, 179 (1967), affords the title compound (XV) identical with the product of Example 1 1.

EXAMPLE 15 l3-Methyl-5,10-(lminomethano)-5 H-Dibenzo[a,d ICyclohepten-l l( H )-one (1, R and R 0, R H and R CH Method A:

A solution of lO-methoxy-Sl-l-dibenzo[a,d]cyclohe pten-S-amine (1!, 1.7 g, 0.007 mole), prepared as described in Example 2 or 8, acetaldehyde (1.4 g, 0.032 mole) and concentrated hydrochloric acid (1.7 ml) in 1,2-dimethoxyethane (350 ml) is refluxed, with stirring, for 1 hour. The mixture is cooled and filtered. The collected precipitate is washed with ether to give the title compound in the form of its corresponding hydrochloric acid addition salt, m.p. 244245C (dec.), which is crystallized from ethanol-ether without change in m.p.; 'y 1685 cm (ketone); A J 290 mp. (e 1650); nmr (DMSO), 2.33 (8-1-1, aromatic, m); 3.93 (1-H at C-5, s);5.50(1-H at C-10, d); 6.05 (l-H at C-1 3, m); 8.63 (CH This hydrochloride acid addition salt may be decomposed to its corresponding free base, m.p. l44-145C, mu- 1,682 cm", by conventional means such as dissolution in chloroform, washing of the chloroform,

solution with 5 percent aqueous sodium bicarbonate,

followed by concentration of the chloroform solution. Method B:

Concentrated hydrochloric acid (0.4 ml) is added to a stirred solution of 5,l1-dihydro-10-oxo-l0H- dibenzo[a,d-cyclohepten-5-amine (1X, 0.4 g, 0.0018 mole, prepared as described in Example 12, and acetaldehyde (0.4 ml, 0.007 mole) in 1,2-dimethoxyethane, the reaction is allowed to proceed at room temperature for 20 minutes and the solution is then refluxed for 1 Vs hours. The solution is taken to dryness, to yield the title compound identical to the product (free base) obtained by Method A above.

EXAMPLE 16 By following the procedures of either Method A or Method B of Example 15 but using as the starting aldehyde, formaldehyde or paraformaldehyde, instead of acetaldehyde, 5,l0-(iminomethano)-5H-dibenzo[ a,d]cyclohepten-l 1(l0H)-one (l, R and R O and both R and R H), is obtained, m.p. 142-l43C. The corresponding hydrochloride acid addition salt of this product has m.p. 270C.

Also according to the foregoing procedures the following compound of formula 1 may be prepared.

Product, (prefix listed below)- 5 .10 Example Starting Material (iminomethano)-5H- dibenzo[a,d]- (Aldehyde cyclohepten- 1 l( 10H )-one 17 propionaldehyde l3-ethyl l 8 butyrukdehyde l 3-propyl 19 Z-phenylacetaldehyde l 3-benzyl 20 3-phenylpropionaldehyde 1 3-phenethyl 21 benzaldehyde 13 phenyl EXAMPLE 22 12-Methyl-5,10-(iminomethano)-5H-dibenzo[a,d] Cycloheptene-l 1(10H)-one (l, R and R O, R CH and R H) 5,lO-(lminomethano)-5H-dibenzo[a,d]cycloheptenll(l0H)-one (l, R and R O and both R and R= H, 1.0 g), prepared as described in Example 16, and sodium hydride (190 mg, 55 percent dispersion in oil) in dry benzene (80 ml) is boiled for 30 minutes and then treated with the organic halide, methyl iodide (2 ml). After boiling for an additional 2 hours, the reaction mixture is cooled and treated with ice water (250 ml). The organic phase is separated, dried over magnesium sulfate, and evaporated. The residue is recrystallized from benzene and then ethanol to afford the title compound. 33 1678, 1,594 and 1,489 cm".

The product of this Example is further characterized by its oxalic acid addition salt, m.p. --197C.

EXAMPLE 23 l2-phenethyl-, 12-trimethoxybenzyl-, 12- dimethylaminoethyl-, l2-diethylaminoethy1-, l2- diisopropylaminopropyl-, l2-pyrrolidinoethyl-, 12-

piperidinoethyl-, 12-(4'-methylpiperidinoethyl)-, 12- (4'-phenylpiperazinoethyl)- and l2-morpholinoethyl- 5, lO-(iminomethano)-5H-dibenzo [a, d] -cycloheptenl 1(10H) -ories, are obtained.

EXAMPLE 24 allyl-, l2-cyclopropylmethyl-, l2-benzyl-, l2- phenethyl-, l2-trimethoxybenzyl, l2- dimethylaminoethy1-, l 2-diethylaminoethy1-, l2- diisopropylaminopropyl-, l2-pyrrolidinoethy1-, 12-

piperidinoethyl-, l2-(4'-methylpiperidinoethyl)-, 12- (4'-phenylpiperazinoethyl)- and l2-morpholinoethylderivatives of l3-methyl-, 13-ethyl-,l3-propyl-, l3- benzyl-, 13-phenethyland l3-phenyl-5 ,10- (iminomethano)-5H-dibenzo[a,d]1l(l0H)-one.

EXAMPLE 25 10,1 l-Dihydro-l l-Hydroxy-l2-Methyl-5,l0- (lminomethano)-5H-Dibenzo[a,d]Cycloheptene (l, R and R H R CH and R OH) 7 To a stirred solution of l2-methyl-5,l( (iminomethano)-5H-dibenio [a,d] 11 (lI-l)-one(l,R and R O and both R and R H, 4.8 g), prepared as described in Example 22, in methanol (100 ml), sodium borohydride (2.0 g) is added.

The mixture is stirred for 3 hours, concentrated to one-third volume, diluted with water and extracted with chloroform. The chloroform extract is washed with brine, dried, and concentrated to dryness, to yield the title compound, 'y 3,500 cm".

EXAMPLE 26 1n the same manner as described in Example 25, except using respectively an equivalent amount of the products obtained in Example 15 to 21 inclusive and 23 and 24 instead of l2-methyl-l0,ll-dihydro-5,l0- (iminomethano)-H-dibenzo[a,d]cyclohepten-l l-( H)-one, there is obtained respectively, l3-methyl- 10,11-dihydro-5,lO-(iminomethano)-5H-dibenzo[a,d lcyclohepten-l l-ol, 10,1 l-dihydro-5,10- (iminomethano)-5H-dibenzo[a,d] l l-ol, the l3-ethyl-, l3-propyl-, l3-benzyl-, l3-phenethyl-, and 13-phenyl derivatives of 10,1 l-dihydro-5,l0- (iminomethano)-5H-dibenzo[a,d]l l-ol, and the l2-methyl-, l2-ethy1-, l2-propy1, l2-allyl-, l2- cyclopropylmethyl-, l2-benzyl-, l2-phenethyl-, l2- trimethoxy-benzyl-, l2-dimethylaminoethyl-, l2- diethylaminoethyl-, l2-diisopropylaminopropyl-, l2- pyrrolidinoethy1-, l2-piperidinoethyl-, l2-(4'-methylpiperidinoethyl)-, l2-(4'-phenylpiperazimoethyl)- and l2-morpholinoethyll 0,1 l-dihydro-S, l 0- (iminomethano )-5H-dibenzo[a,d]cyclohepten-l l-ol, and the l2-methyl-, l2-ethyl-, l2-propy1, l2-alkyl-, l2- cyclopropylmethyl-, l2-benzyl-, l2-phenethyl-, l2- trimethoxybenzyl, l2-dimethylaminoethyl-, l2- diethylaminoethyl-, l2-diisopropylaminopropyl-, l2- pyrrolidinoethyl-, l2-piperidinoethyl-, l2-(4-methylpiperidinoethyl)-, l2-(4'-phenylpiperazinoethyl)- and l2-morpholinoethylderivatives of l3-methyl-, l3- ethyl-, l3-propyl-, l3-benzyl-, 13-phenethyland 13- phenyl-l0,l l-dihydro-5,l0-(iminomethano)-5H- dibenzo[a,d]-cyclohepten-l l-ol.

EXAMPLE 21 The ll-acctoxy-, l l-propionoxyand l l-butyryloxyderivatives of 10,11-d1hydro-5,l0-(iminomethano)-5 H-dibenzo[a,d]1l-ol and the l3-methyl-, l3-ethyl-, l3-propyl-, l3-benzyl-, l3-phenethyland l3-phenylderivatives thereof, may be prepared by allowing the corresponding 1 l-hydroxy derivative, prepared as described in Example 26, 5 molar equivalents of gaseous hydrobromic acid and 50 molar equivalents of the respective appropriate acid, acetic, propionic or butyric acid, to stand at room temperature for 24 hours, followed by dilution with water, extraction of the mixture with benzene, washing of the benzene extract with 5 percent aqueous sodium bicarbonate and evaporation of the extract.

EXAMPLE 28 The ll-acetoxy-, l l-propionoxyand ll-butyryloxyderivatives of l2-methyl-, 12-ethyl-, l2-propyl-, 12-

al1yl-, l2-cyclopropylmethyl-, 12-benzyl-, l2- phenethyl-, l2-trimethoxybenzyl-, 12- dimethylaminoethyl-, l2-diethylaminoethyl-, l2- diisopropylaminopropyl-, 12-pyrro1idinoethyl-, l2-

piperidinoethyl-, 12-(4-methylpiperidinoethyl)-, l2- (4-phenylpiperazinoethyl)- and l2 n1orpholinoethyl- 10,1l-dihydro-S,10-(iminomethano)-5l-l-dibenzo[a,d ]cyclohepten-l l-ol, and the l2-methyl-, l2-ethyl-, 12- propyl-, l2-allyl-, l2-cyclopropylmethyl-, l2-benzyl-, l2-phenethyl-, l2-trimethoxybenzyl-, l2- dimethy1aminoethyl-, 12-diisopropylaminopropyl-, 12- pyrrolidinoethy1-, 12-piperidinoethyl-, l2-(4'-methylpiperazinoethyl)-, l2-(4'-phenylpiperazinoethyl)- and l2-morpholinoethylderivatives of l3-methyl-, l3- ethyl-, l3-propyl-, l3-benzyl-, l3-phenethyland 13- phenyl-l0,ll-dihydro-5,l0-(iminomethano)-5H- I dibenzo[a,d]cyclohepten-l l-ol may be prepared by allowing a solution of the corresponding ll-hydroxy derivative, prepared as described in Examples 25 and 26, 20 molar equivalents of the respective appropriate acyl anhydride, acetic, propionic or butyric anhydride, and 50 molar equivalents of pyridine, to stand at room temperature for 24 hours, followed by evaporation of the reaction mixture under reduced pressure on a steam bath.

EXAMPLE 29 The ll-methoxy-, ll-ethoxy, and ll-propoxy derivatives of 10,1l-dihydro-5,lO-(iminomethano)-5 H-dibenzo[a,d]cyclohepten-ll-ol and the l3-methyl-, l3-ethyl-, l3-propyl, l3-benzyl-, l3-phenethyland l3-phenylderivatives thereof, may be prepared by allowing a solution of the corresponding 1 l-keto derivative, prepared as described in Example 15 to 21 inclusive, l0 molar equivalents of acetyl chloride and 50 molar equivalents of pyridine to stand at room temperature for 24 hours, followed by evaporation of the mixture under reduced pressure on a steam bath, dissolving the residue in molar equivalents of methanol, stirring the methanolic solution with 10 molar equivalents of sodium borohydride for 3 hours, followed by concentration of the mixture to one-third volume, dilution with water, extraction of the mixture with chloroform, evaporation of the chloroform extract to give the corresponding 1 l-hydroxy-N-acetyl derivative of formula 1, followed by treatment of last said EXAMPLE 30 The ll-methoxy-, ll-ethoxy-, and ll-propoxyderivatives of l2-methyl-, 12-ethyl-, 12-propyl-, l2-

allyl-, l2-cyc1opropylmethyl-, l2-benzy l-, l2- phenethyl-, 12-trimethoxybenzyl, 12- dimethylaminoethyl-, l2-diethylaminoethy1-, 12- diisopropylaminopropyl-, l2-pyrrolidinoethyl-, 12-

piperidinoethyl-, l2-(4'-methy1piperidinoethyl)-, 12- (4'-phenylpiperazinoethyl)- and 12- morpholinoethyl- 10,1 l-dihydro-5,10-(iminomethano)-5H-dibenzo[a,d] cyclohepten-ll-ol, and the l2-methyl-, 12-ethyl-, 12- propy1-, 12-allyl-, l2-cyclopropylmethyl-, l2-benzyl-,

12-phenethyl-, 12-trimethoxybenzyl-, 12- dimethylaminoethyl-, l2-diethylaminoethyl-, 12- diisopropylaminopropyl-, l2-pyrrolidinoethyl-, 12-

piperidinoethyb, l2-(4-methylpiperazinoethyl)-, 12- (4'-phenylpiperazinoethyl)- and 12-morpholinoethylderivatives of 13-methyl-, 13-ethyl-, 13-propyl-, 13- benzyl-, 13-phenethyland 13-phenyl-l0,1l-dihydro- 5,lO-(iminomethano)-5H-dibenzo[a,d]cycloheptanl l-ol may be prepared by treatment of the appropriate corresponding ll-hydroxy derivative, prepared as described in Examples 25 and 26, according to the manipulative procedure of Example 22 using the appropriate organic halide, methyl iodide, ethyl chloride or propyl iodide.

The ll-methoxy derivative of l2-methyl-l0,1ldihydro-5,10-(iminomethano)-5H-dibenzo[a,d ]cyclohepten-1 l-ol, 10,1 1 -dihydro-1 l-methoxyl 2 methyl-5,10-(iminomethano)-5H-dibenzo[a,d]- cycloheptene (1, 11 and R both H, R OCH; and R CH has 735 2,810, 1,470 and 1,090 cm". its corresponding hydro-chloride acid addition salt has m.p. 245-248C. after recrystallization from methanol.

EXAMPLE 3 r 10,! l-Dihydro-l 1-pyrrolidino-5,l0-(iminomethano 5H-dibenzo[a,d]-cycloheptene (l, R, R and R H and R pyrrolidino) A solution of the 1 l hydroxy-N-acetyl derivative of formula I, 10,11-dihydro-5,l-(iminomethano)-5H- dibenzo[a,d-cyclohepten-1 l-ol N-acetate (7.8 g), prepared as described in Example 29, in 60 ml of pyridine is treated with 7.8 g p-toluenesulfonyl chloride at C. The mixture is then allowed to stand at room temperature for 24 hours. The mixture is then diluted with water and extracted with ether. The ether extract is washed successively with percent aqueous hydrochloric acid and 5 percent sodium carbonate solution, dried, and evaporated to dryness. The residue is dissolved in 200 ml of acetone and the resulting solution is stirred with 5.0 g of lithium bromide at 50C for 5 hours. The reaction mixture is concentrated to onefourth of its volume, diluted with water and extracted with chloroform. The chloroform extract is dried, evaporated to dryness. The residue is dissolved in 25 ml of pyrrolidine and the solution boiled for 1 hour. Con centration of the reaction mixture under reduced pressure on a steam bath yields the residue which is redissolved in chloroform. The chloroform solution is washed with water, dried and evaporated to dryness. The resulting residue is boiled for 6 hours in a solution of sodium hydroxide (8 g), water (30 ml) and ethanol (250 ml) for 6 hours. The solution is evaporated to dryness and the residue diluted with water and extracted with chloroform. The chloroform extract is dried and evaporated to yield the title compound, 5,5 2,790, 1,500, 1,453,and 1,100 cm.

EXAMPLE 32 [n the same manner as described in Example 31, but using an equivalent amount of the 13-methy1-, l3- ethyl-, l3-propyl-, 13-benzyl-, l3-phenethylor 13- phenyl-10,1 l-dihydro-5,10-(iminomethano)-5H- dibenzo[a,d]cyclohepten-1l-ol N-acetate, prepared as described in Example 29, instead of 10,1l-dihydro- 5,10-(iminomethano)-51-l-dibenzo[a,d]cyclohepten- 11-01, the corresponding 13-methyl-, 13-ethyl-, l3- propyl-, l3-benzyl-, l3-phenethyland 13-phenyl- 10,11-dihydro-1 1-pyrrolidino-5,10-(iminomethano)- 5H-dibenzo[a,d]cycloheptenes are obtained, respectively.

EXAMPLE 33 in the same manner as described in Example 31 and using the appropriate ll-hydroxy-N-acetyl derivative of formula 1, 10,1 1-dihydro-5,10-(iminomethano)-5H- dibenzo[a,dcyclohepten-1l-ol N-acetate, or its 13- methyl-, l3-ethyl-, 13-propyl-, 13-benzyl-, l3- phenethylor l3-phenylderivatives, prepared as described in Example 29, together with the appropriate secondary amine, dimethylamine, diethylamine, (note: when using the latter two amines, the reaction is performed in a sealed pressurized vessel at C, at minimum amount of toluene is employed as a solvent for the secondary amine), piperidine, or morpholine, instead of pyrrolidine, the 11-dimethy1amino-, lldiethylamino-, 1l-piperidino and 11- morpholinoderivatives of 10,11-dihydro-5,l0-(iminomethano)-5 H-dibenzo[a,d]cyc1oheptene and the 13-methyl-, l3- ethyl-, l3-propyl-, 13-benzyl-, IS-phenethyland 13- phenylderivatives thereof, are obtained.

EXAMPLE 34 10,1 l-Dihydrol Z-methyl- 1 l-pyrrolidino-5,l0- (iminomethano)-5H-dibenzo[a,d]cycloheptene (I, R and R both H, R pyrrolidino and R =CH In the same manner as described for Example 31, but using an equivalent amount of 10,1 l-dihydro-12- methyl-5,10-(iminomethano)-5H-dibenzo[a,d lcyclohepten-l l-ol, prepared as described in Example 25, instead of 10,11-dihydro-5,10-(iminomethano)-5 H-dibenzolQa,dlcyclohepten-1l-ol N-acetate, and foregoing the final treatment with boiling aqueous sodium hydroxide in the ethanol, the title compound, m.p. 106-107C, may be obtained after purification by elution from a column of neutral alumina (activity Ill), with benzeneechloroform (3:1) and recrystallization from ethanol.

- EXAMPLE 35 EXAMPLE 36 In the same manner as described in Example 32 but using an equivalent amount of the ll-hydroxy compound of formula I, l2-ethyl-, l2-propyl-, l2-allyl-, l2- cyclopropylmethyl-, l2-benzyl-, l2-phenethyl-, l2- trimethoxybenzyl-, 12-dimethylaminoethyl-, 12- diethylaminoethyl-, l2-diisopropylaminopropyl-, l2- pyrrolidinoethyl-, l2-piperidinoethyl-, l2-(4'-methylpiperazinoethyl)-, l2-(4-phenylpiperazinoethyl)-, or l2-morpholinoethylderivatives of lO,ll-dihydro- 5,lO-(iminomethano)-5H-dibenzo[a,d]cycloheptenll-ol and the l3-methyl-, l3-ethyl-, 13-propyl-, l3- benzyll3-phenethylor l3-phenyl derivatives thereof, prepared as described in Example 26, the corresponding l2-ethyl-, l2-propyl-, l2-allyl-, l2-cyclopropylmethyl-, l2-benzyl-, 12-phenethyl-, l2 trimethoxybenzyl-, l2-dimethylaminoethyl-, 12- diethylaminoethyl-, l2diisopropylaminopropyl-, l2- pyrrolidinoethyl-, l2-piperidinoethyl-, l2-(4-methylpiperazinoethyl)-, l2-(4-phenylpiperazinoethyl)-, and 12-morpholinoethylderivatives of ll-pyrrolidino- 10,] 1-dihydro-5,lO-(iminomethano )-5H-dibenzo[a,d]- cycloheptene and l3-methyl-, 13-ethyl-, l3-propyl-, l3-benzyl-, l3-phenethyland l3-phenyl-ll-pyrrolidino-l 0,1 l-dihydro-S l O-(iminomethano )-5H- dibenzo[a,d]cycloheptene, may be obtained, respectively.

EXAMPLE 37 In the same manner as described in Example 32 and using the ll-hydroxy compound of formula I, 12- methyl-, l2-ethyl-, l2-propyl-, l2-al1yl-, l2- cyclopropylmethyl-,. l2-benzyl-, l2-phenethyl-, l2- trimethoxybenzyl-, l2-dimethylaminoethyl-, l2- diethylaminoethyl-, l2-diisopropylaminopropyl-, l2-

morpholine, instead of pyrrolidine, the corresponding 1 l-dimethylamino-, l l-diethylamino-, l l-piperidinoand ll-morpholinosubstituted analogs of the [2- methyl-, l2-ethyl-, l2-propyl-, l 2-allyl-, l2- cyclopropylmethyl-, l2-benzyl-, l2-phenethyl-, l2- trimethoxybenzyl-, l2-dimethylaminoethyl-, l2- diethylaminoethyl-, 12-diisopropylaminopropyl-, l2- pyrrolidinoethyl-, l2-piperidinoethyl-, l2-(4'-methylpiperazinoethyl)-, l2-(4-phenylpiperazinoethyl)- and l2-morpholinoethylderivatives of lO,ll-dihydro- 5,]0-(iminomethano)-5H-dibenzo-[a,d]cycloheptene and of l3-methyl-, l3-ethyl-, l3-propyl-, l3-benzyl-, l3-phenethyl-, and l3-phenyl-l0,ll-dihydro-5,l0- (iminomethano)-5H-dibenzo[a,d]cycloheptene may be obtained.

EXAMPLE 3 8 l0-Cyano-5H-dibenzo[a,d]cyclohepten-5-one A mixture of lO-bromo-SH-dibenzo[a,d]cyclohe pten-S-one (99.0 g), cuprous cyanide (40 g) and quinoline (200 ml) is stirred and heated at l90200C (internal temperature) for 1 hour. The mixture is cooled and the resulting solid mass is broken up and stirred under ether. The mixture is filtered and the solids are washed with ether. The remaining solids are triturated under chloroform. The mixture is filtered and the solids are washed with hot chloroform. The green insoluble residue is discarded.

The ether filtrate and washings are exhaustively washed with 2N HCl, then water, and then dried and EXAMPLE 39 5, l 0-Epoxymethano-l0,l ldihydro-5H-dibenzo[a,d ]cyclohepten-l 3-one lO-Cyano-SH-dibenzo[a,d]cyclohepten-5one (5.0 g), prepared as described in Example 38 is suspended in ethanol ml) and sodium borohydride (2.5 g) is added. The mixture is stirred at room temperature overnight and then refluxed for two hours. The mixture is cooled, treated with 2N HCl and evaporated to small volume. The solids are collected, washed with water and dried to give a solid. This material is dissolved in chloroform (minimum volume) and chromatographed on alumina. Benzene elutes the title product which crystallizes from methanol as needles, m.p. l48-l50 C. j

The title product is also obtained when the above procedure is followed except that dimethyl sulfoxide (20 ml) is used in place of ethanol (80 ml). EXAMPLE 40 A mixture of 5,10-(epoxymethano)-l0,l l-dihydro-S H-dibenzo[a,d]cyclohepten-13-one (1.l2 g) prepared as described in Example 39, and ammonium hydroxide (100 ml; d 0.88) is heated for 7 hours at 190C.

The solid product is collected and dried and crystallized from ethanol to give the title product, m.p. 227-229C. EXAMPLE 41 1n a similar manner to that described in Example 40, but using methylaminc, ethylamine, propylaminc, allylamine, cyclopropylmethylamine, benzylaminc, penethylaminc, trimethuxybenzylamine, dimethylaminoethylamine, diethylaminoethylaminc, diisopropylaminopropylamine, pyrrolidinoethylamine, piperidinoethylamine, 4'-methylpiperazinoethylamine, 4-phenylpiperazinoethylamine, or morpholinoethylamine in place of ammonia, the corresponding l2-methyl-, 12-ethyl-, l2-propy1-, 12-ally1-, l2-cyclopropylmethyl-, l2-benzyl-, 12-phenethyl-, l2trimethoxybenzyl-, 12-dimethylaminoethyl-, 12- diethylaminoethyl-, 12-diisopropylaminopropyl-, 12- pyrrolidinoethy1-, l2-piperidinoethyl-, l2-(4-methylpiperazinoethyl)-, l2-(4'-phenylpiperazinoethyl)-, or I 2-morpholinoethyl- 10,1 1 -dihydro-5, 1 (iminomethano)-H-dibenzo[a,d]cyclohepten-13-one is obtained.

Alternatively, a mixture of 10,1 1-dihydro-5,l0- (iminomethano)-51-1-dibenzo[a,d]cyclohepten-l3-one (23.7 g), prepared as described in Example 40, anhydrous benzene (250 ml) or anhydrous dioxane (250 ml), sodium hydride (5.0 g of a 52 percent suspension in mineral oil) and either methyl-, ethyl-, propyl-, allyl-, cyclopropylmethyl-, benzy1-, phenethyl-, trimethoxybenzyl-, dimethylaminoethyl-, diethylaminoethyl-, diisopropy1aminopropyl-, pyr rolidinoethyl-, piperidinoethyl-, 4'-methylpiperazinoethyl-, 4'-phenylpiperazinoethyl-, morpholinoethyl chloride, bromide or iodide (0.12 mole) is stirred and heated under reflux for 18 hours. The mixture is evaporated to dryness and the residue is washed with water and then with pentane to leave the corresponding l2-methyl-, l2-ethyl-, 12' propyl-, 12-allyl-, l2-cyclopropylmethyl-, l2-benzyl-,

l2-phenethyl-, 12-trimethoxybenzy1-, l2- dimethylaminoethyl-, l2-diethylaminoethyl-, 12- diisopropylaminopropyl-, l2-pyrrolidinoethyl-, l2-

piperidinoethyl-, l2-(4'-methylpiperazinocthyl)-, l2- (4'-phenylpiperazinoethyl-, or 12-morpholinoethyl- 10,1 l-dihydro-5,10-(iminomethano)-5H-dibenzo[a,d lcyclohepten-13-one is obtained.

EXAMPLE 42 1 l-Bromo-l0,l l-dihydro-l2-methyl-5,l0- (iminomethano)s5H-dibenzo[a,d]-cyclohepten-13-one (XXII, R CH A suspension of 12methy1-l0,1l-dihydro-5,10- (iminomethano)-5H-dibenzo[a,d]cyclohepten-1 3-one (XXI, R CH 15.11 g), m.p. 23924lC, prepared as described in Example 41, and N-bromosuccinimide (11.4 g) in carbon tetrachloride (300 ml) containing about 50 mg of benzoyl peroxide is boiled for 75 minutes. The mixture is filtered and the filtrate evaporated to dryness. The residue is crystallized from ethyl acetate to yield the title compound, m.p. 205-20 7C, vgg 1,670 cm.

EXAMPLE 43 1n the same manner as described in Example 42, but using an equivalent amount of 12-ethy1-, l2-propyl-, 12-cyclopropylmethyl-, 12-benzyl-, l2-phenethyl-, 12- trimethoxybenzy1-, l2-dimethylaminoethyl-, l2- diethylaminoethy1-, 12-diisopropylaminopropyl-, l2- pyrrolidinoethyl-, 12-piperidinoethyl-, l2-(4'-methy1- piperazinoethyl)-, l2-(4'-phenylpiperazinoethyl)-, or l2-morpholinoethyl-10,1 l-dihydro-5,10- (iminomethano)-5H-dibenzo[a,d]cycloheptenl 3-one, prepared as described in Example 41, in place of 12- methy1l0,l l-dihydro-5,l0-(iminomethnno)-5H- dihenzo!a,d]cyclohepten-Ill-one, the corresponding l2-ethyl-, l2-propyl-, l2-cyclopropylmcthyl-, l2- benzyl-, l2-phenethyl-, l2-trimethoxybenzyl-, 12- dimethylaminoethyl-, l2-diethylaminoethyl-, 12- diisopropylaminopropyl-, 12-pyrrolidinoethyl-, l2-

piperidinoethyl-, 12-(4'-methylpiperazinoethyl)- and l2-morpholinoethyl-l l-bromo-10,1 1-dihydro 5 ,10- (iminomethano)-5H-dibenzo[a,d]cyclohepten-13-one may be obtained, respectively.

EXAMPLE 44 10,1 l-Dihydro-l l-methoxy-l 2-methyl-5,l0- (iminomethano)-5 H-dibenzo[a,d]cyclohepten-13-one (XXlll, R CH A solution of l l-bromo-l0,l l-dihydro-l Z-methyl- 5,10-(iminomethano)-5H-dibenzo[a,d]cycloheptenl 3 -one (XXII, R CH;,; 6.7 g), prepared as described in Example 42, in 13.4 ml of a solution of sodium methoxide, prepared by dissolving 3.5 g of sodium in m1 of methanol), is stirred and boiled for 18 hours. The reaction mixture is concentrated, diluted with water and extracted with chloroform. The chloroform extract is dried, and then concentrated to dryness. Crystallization of the residue from isopropanol affords the title compound, m.p. l93C.

EXAMPLE 45 benzyl-, 12-phenethyl-, 12-trimethoxybenzyl-, l2- dimethylaminoethyl-, 12-diethylaminoethyl-, l2- diisopropylaminopropyl-, l2-pyrro1idinoethyl-, l2-

piperidinoethy1-, l2-(4'-methylpiperazinoethyl)-, 12-

(4'-phenylpiperazinoethyl)- and 12 morpholinoethyl- 10,1 l-dihydro-l 1-methoxy-5,lO-(iminomethano)-5H- dibenzo[a,d]-cyclohepten-l3-one may be obtained, respectively.

EXAMPLE 46 By substituting an equivalent amount of'sodium ethoxide solution or sodium propoxide solution for sodium methoxide solution in the procedures of Examples 44 or 45, the corresponding l1-ethoxyand 11- propoxy-, instead of ll-methoxy, derivatives of the products listed in said Examples may be obtained, respectively.

EXAMPLE 47 10,1 l-Dihydro-l l-methoxy-l 2-methyl-5,10- (iminomethano)-5H-dibenzo-[a,d]cycloheptene (I, R and R both H, R OCH;, and R CH,,)

Lithium aluminum hydride (1.2 g) is added portionwise to a solution of 10,1 l-dihydro-l l-methoxy-IZ- methyl-5 l -(iminomethano)-5H-dibenzo[a,d]cyclohe pten-l 3-one (XXIII, R CH 3.5 g), prepared as described in Example 44, in anhydrous tetrahydrofuran. The mixture is boiled for hours. Excess reagent is decomposed by careful addition of water. The mixture is filtered and the filtrate is concentrated to dryness to yield the title compound, 5,5 2,810, 1,470 and 1,090 cm", identical to the product obtained in Example 30.

This product is characterized further as its corresponding hydrochloric acid addition salt, m.p. 245-248C after recrystallization from methanol.

EXAMPLE 48 EXAMPLE 49 By substituting an equivalent amount of the appropriate ll-ethoxy or ll-propoxyderivatives described in Example 46 in place of 10,1 l-dihydro-l lmethoxy-12-methy1-5 ,10-(iminomethano)-5H- dibenzo[a,d]cyclohepten-13-one in Example 47, the lI-ethoxyor ll-propoxyderivatives of l2-methyl-,

12-ethyl-, l2-propyl-, l2-cyclopropylmethyl-, l2- benzyl-, 12-phenethyl-, l2-trimethoxybenzyl-, l2 dimethy1aminoethyl-, 12-diethy1aminoethyl-, 12- diisopropylaminopropyl-, 12-pyrrolidinoethyl-, 12- piperidinoethyl-, l2-(4'-methylpiperidinoethyl l2- (4'-phenylpiperazinoethyl)- or 12-morpholinoethyl 10,1 l-dihydro-S,l0-(iminomethano)-5H-dibenzo[a,d ]cycloheptene may be obtained.

EXAMPLE so 10,11-Dihydro-ll-hydroxy-l2-methyl-5,l0- (iminomethano)-5H-dibenzo-[a,d]cycloheptenl 3-one (XXIII, R CH R H).

A mixture of l1-bromo-10,l l-dihydro-lZ-methyl- 5,10-(iminomethano)-5H-dibenzo[a,d]cyclohepten-13 -one (0.5 g), prepared as described in Example 42, dioxane (10 ml), potassium hydroxide (0.1 g), and water (2.0 m1) is heated under reflux and stirred for 3 hours. The mixture is evaporated, diluted with water, and the precipitate is crystallizedfrom methanol to give the title product m.p. 259-261C, y 3,435, 1,658 cm".

EXAMPLE 51 In the same manner as described in Example 50, but using an equivalent amount of 12-ethyl-, l2-propyl-, l2-cyclopropylmethyI-, 12-benzyl-, 12-phenethyl-, l2- trimethoxybenzyl-, l2dimethylaminoethyl-, l2- diethylaminoethyl-, 12-diisopropylaminopropyl-, 12- pyrrolidinoet hyb, l2-piperidinoethyl-, l2-(4-methylpiperazinoethyl)-, l2-(4-phenylpiperazinoethyl)-, or l2-morpholinoethyl-1 1-bromo-10,1 1-dihydro-5,10- (iminomethano)-5H-dibenzo[a,d]-cyclohepten-13- one, prepared as described in Example 43, in place of 1 1-br0m0-l0,l 1-dihydro-12-methyl-5,l0- (iminomethan0)-5H-dibenzo[a,d]cycloheptenl 3-one,

the corresponding 12-ethyl-, 12-propyl-, l2- cyclopropylmethyl-, l2-benzyl-, l2-phenethyl-, l2- trimethoxybenzyl-, l2-dimethylaminoethyl-, 12-

diethylaminoethyl-, 12-diisopropylaminopropyl-, l2- pyrrolidinoethyl- 12-piperidinoethyl-, 12-(4'-methylpiperazinoethyl)-, 12-(4'-phenylpiperazinoethyl)- and 12-morpholinoethyl-10,1 l-dihydro-l l-hydroxy-5,10-

(iminomethano)-5H-dibenzo[a,d]cyclohepten-13-one may be obtained; respectively.

EXAMPLE 52 10,1 l-Dihydro-l l-hydroxy-l2-methyl-5,10- (iminomethano)-5 H-dibenzo-[a,d]cycloheptene (l, R and R both H, R OH and R CH EXAMPLE 53 In the same manner as described in Example 52, but using an equivalent amount of 12-ethyl-, l2-propyl-, 12-cyclopropylmethyl-, l2-benzyl-, l2-phenethyl-, 12- trimethoxybenzyl-, 12-dimethylaminoethyl-, l2- diethylaminoethyl-, lZ-diisopropylaminopropyl-, 12- pyrrolidinoethyl-, 12-piperidinoethyl-, 12-(4'-methyl- EXAMPLE 54 10,1 l-Dihydro-l Z-methyl-l l-pyrrolidino-5,l- (iminomethane-l-l-dibenzo-[a,d]cycloheptenl 3-one (XXIV, R CH and NR R pyrrolidino) A mixture of ll-bromo-l0,l l-dihydro-lZ-methyl- 5, l 0-(iminomethano)-5H-dibenzo[a,d]cyclohepten-l 3 -one (XXll, R CH 4.7 g), prepared as described in Example 42, and pyrrolidine is boiled for 1 hour. The reaction mixture is concentrated to dryness and the residue dissolved in water. The aqueous solution is extracted with chloroform. The extract is dried and evaporated. The residue is recrystallized from ethanol to give the title compound, m.p. l89-l92C; )t,,,,,,' 277 mp. (e=l,470) and 268 my. (e=l9l0).

EXAMPLE 55 In the same manner as described in Example 54 but using an equivalent amount of l2-ethyl-, l2-propyl-, l2-cyclopropylmethyl-, l2-benzyl-, 12-phenethyl-, l2- trimethoxybenzyl-, l2-dimethylaminoethyl-., l2- diethylaminoethyl-, l2-diisopropylarninopropyl, l2- pyrrolidinoethyl-, l2-piperidinoethyl-, l2-(4'-methy1- piperazinoethyl)-, l2-(4'-phenylpiperazinoethyl)-, or l2-morpholinoethyl-l l-bromo- 10,1 l-dihydro-5,l0- (iminomethano)-5H-dibenzo[a,d]wyclohcpten-l 3- one, prepared as described in Example 43, in place of l l-bromo-l0,l l-dihydro-l2-methyl-5,l0- (iminomethano)-5H-dibenzo[a,d]cyclohepten-l 3'-one,

the corresponding l2-ethyl-, 12-propyl-, l2- cyclopropylmethyl-, l2-benzyl-, l2-phenethyl-, l2- trimethoxybenzyl-, l2-dimethylaminoethyl-, l2-

diethylaminoethyl-, l2-diisopropylaminopropyl-, l2- pyrrolidinoethyll 2-piperidinoethyl-, l2-( 4'-methylpiperazinoethyl)-, l2-(4'-phenylpiperazinoethyl)- and l2-morpholinoethyll 0,1 l-dihydro-l l-pyrrolidino- 5 l 0-( iminomethano )-5H-dibenzo[a,d]cyclohepten l 3 -one may be obtained, respectively.

EXAMPLE 56 By substituting an equivalent amount of the secondary amines, dimethylamines, diethylamine, piperidine or morpholine, for pyrrolidine in the procedures of Example 54 or 55, the corresponding ll-dimethylamino-, diethylamino-, ll-piperidino-and l l-morpholino-, instead of ll-pyrrolidino-, derivatives of the products listed in said Examples may be obtained, respectively. Note that when dimethylamine and diethylamine are employed in the method of this Example, the reaction is performed in a sealed, pressurized vessel at "C with a minimum amount of toluene being employed as a solvent for the secondary amine.

EXAMPLE 57 10,1l-Dihydro-lZ-methyl-l l-pyrrolidino-5,l0- (iminomethano)-5H-dibenzo-{a,d]cycloheptene (l, R and R H, R pyrrolidine and R =CH A solution of 10,1l-dihydro-lZ-methyl-l l-pyrrolidino-S, l0-(iminometh'ano)-5H-dibenzo[ a,d}cyclohepten-l3-one (3.3 g), prepared as described in Example 54, in anhydrous tetrahydrofurna (30 ml) is added dropwise to a stirred suspension of lithium aluminum hydride (3.3 g) in anhydrous tetrahydrofurna (30 ml). The mixture is boiled for 4 hours, cooled and then treated cautiously with water-tetrahydrofuran (1:4, 100 ml). The mixture is filtered. The filtrate is evaporated. The residue is dissolved in ether. The ether solution is washed with brine, dried, and evaporated. The residue is subjected to chromatography on neutral alumina (activity=lll). Elution with benzenechloroform (3:1) and subsequent recrystallization of the eluate from ethanol gives the title compound, m.p. l06"107C, identical with the product of Example 34.

EXAMPLE 58 EXAMPLE 59 In the same manner as described in Example 57 but using an equivalent amount of the l1-dimethylamino-, ll-diethylaminoll-piperidinoor ll-morpholinoderivatives of l2-methyl-, l2-ethyl-, l2-propyl-, l2- cyclopropylmethyl-, l2-benzyl-, l2-phenethyl-, l2- trimethoxybenzyl-, l2-dimethylaminoethyl-, l2- diethylaminoethyh, lZ-diisopropylaminopropyl-, l2- pyrrolidinoethyl-, l2-piperidinoethyl-, l2-(4'-methyl piperazinoethyl)-, l2-(4'-phenylpiperazinoethyl)-, or l2-morpholinoethyl-l0,l l-dihydro-S, l 0- (iminomethano)-5H-dibenzo[a,d]cyclohepten-l3-one,

prepared as described in Example 56, the corresponding 1 l-dimethylamino-, l l-diethylamino-, l 1- piperidinoor lI-morpholinoderivatives of 12- methyi-, l2-ethyl-, l2-propyl-, l2-cyclopropylmethyl-,

l2-benzyl-, l2-phenethyl-, l2-trimethoxybenzyl-, l2 dimethylaminoethyl-, l2-diethylaminoethyl-, l2- diisopropylaminopropyl-, l2-pyrrolidinoethyl-, 12- piperidinoethyl-, l2-(4'-methylpiperazinoethyl)-, l2- (4-phenylpiperazinoethyl)-, or l2-morpholinoethyl- 10,1 l-dihydro-S l O-(iminomethano )-5l-l-dibenzo[a,d ]cycloheptenes may be obtained, respectively.

We claim: I

1. A compound selected from those of the formula wherein R represents hydrogen, lower alkyl having one to four carbon atoms, allyl, cyclopropylmethyl,

benzyl, phenethyl, trimethoxybenzyl, dimethylaminoethyl, diethylaminoethyl, diisopropylaminopropyl, pyrrolidinoethyl,

piperidinoethyl, 4'-methylpiperidinoethyl, 4'phenylpiperazinoethyl and morpholinoethyl; R represents hydrogen, lower alkyl having one to four carbon atoms, benzyl, phenyl and phenethyl; and acid addition salts thereof with pharmaceutically acceptable acids.

2. A compound selected from those of the formula wherein R represents hydrogen or lower alkyl of one to four carbon atoms; R represents hydrogen, lower alkyl of one to four carbon atoms, benzyl, phenyl and phenethyl; and acid addition salts thereof with pharmaceutically acceptable acids.

3. 5 ,10-(lminomethano)-5l-l-dibenzo[a,d]cycloho pten-l l(l0H)-one, as claimed in claim 2.

4. The hydrochloric acid addition salt of 5,10- (iminomethano)-5H-dibenzo[a,d]cyclohepten-l l (H)-one, as claimed in claim 2.

5. l3-Methyl-5 l O-(iminomethano )-5l-ldibenzo[a,d]cyclohepten-l1(10l-l)-one, as claimed in claim 2.

6. The hydrochloric acid addition salt of l3-methyl- 5,l0-(iminomethano)-5H-dibenzo[a,d] cycloheptenll(10l-l)-one, as claimed in claim 2.

7. 13-Ethyl-5 l 0-(iminomethano)-5 H-dibenzo [a,d]-cyclohepten-1 l(10l-l)-one, as claimed in claim 2.

8. 13-Propyl-5 ,l 0-(iminomethano)-5 H-dibenzo [a,d]cyclohepten-l l(10l-l)-one, as claimed in claim 2.

9. 13-Benzy1-5 1 0-(iminomethano)-5 H-dibenzo [a,d]cyclohepten-l l(l0H)-one, as claimed in claim 2.

l0. l3-Phenethyl-5 l O-(iminomethano )-5H- dibenzo[a,d]cyclohepten-11(10Hl-one, as claimed in claim 2.

11. l3-Phenyl-5 l O-(iminomethano)-5H- dibenzo[a,d]cyclohepten-1l(l0H)-one, as claimed in claim 2.

12. l2-Methyl-5, l 0-(iminomethano)-SH- dibenzo[a,d]cyclohepten-ll(l0H)-one, as claimed in claim 2.

13. The oxalic acid addition salt of 12-methyl-5,lO' (iminomethano)-5H-dibenzo[a,d]l 1(l()H)-one, as claimed in claim 2.

14. A compound selected from those of the formula wherein R represents hydrogen and R represents hydroxyl, lower alkoxy having from one to three car bon atoms, dimethylamino, diethylamino, pyrrolidino, piperidino and morpholino; R represents hydrogen, lower alkyl having one to four carbon atoms, allyl, cyclopropylmethyl, benzyl, phenethyl, trimethoxybenzyl, dialkylaminoalkyl having from two to three carbon atoms in the alkyl radical and from one to three carbon atoms in each of the dialkyl radicals, pyrolidinoethyl, piperidinoethyl, 4'-methylpiperazinoethyl, 4'-phenylpiperazinoethyl and morpholinoethyl; and R represents hydrogen, lower alkyl having one to four carbon atoms, benzyl, phenethyl and phenyl; and acid addition salts thereof with pharmaceutically acceptable acids.

15. A compound selected from those of the formula wherein R represents hydrogen, R represents hydroxyl, lower alkoxy having from one to three carbon atoms or pyrrolidino; R represents hydrogen or lower alkyl having one to four carbon atoms; and R represents hydrogen; and acid addition salts thereof with pharmaceutically acceptable acids.

16. 10,1 l-Dihydro-l l-methoxy-l2-methyl-5,l0- (iminomethano)-5H-dibenzo[a,d]cycloheptene, as claimed in claim l5.

17. The hydrochloric acid addition salt of 10,11- dihydro-l l-methoxyl Z-methyl-S l 0-(iminomethano)- SH-dibenzo[a,d]cycloheptene, as claimed in claim l5.

18. 10,1 l-Dihydro-l l-pyrrolidino-5,lO-(iminomethano)-5H-dibenzo[a,dl-cycloheptene. as claimed in claim 15.

l 9. l 0 l 1- l )ihy dro-l2-methyll l-pyrrolidino-S, l0- (iminomethano)- 5 H-dibenzola,dlcycloheptene, as claimed in claim 15.

20. 10,1 l-Dihydro-l l-hydroxy-l 2-methyl-5 l 0- (iminomethano)-5H-dibenzo[a,d]cycloheptene, as claimed in claim 15.

21. The hydrochloric acid addition salt of 10,11- dihydro-l l-hydroxyl 2-methyl-5 l O-(iminomethano SH-dibenzo [a,d]cycloheptene, as claimed in claim 15. 

1. A compound selected from those of the formula wherein R3 represents hydrogen, lower alkyl having one to four carbon atoms, allyl, cyclopropylmethyl, benzyl, phenethyl, trimethoxybenzyl, dimethylaminoethyl, diethylaminoethyl, diisopropylaminopropyl, pyrrolidinoethyl, piperidinoethyl, 4''-methylpiperidinoethyl, 4''phenylpiperazinoethyl and morpholinoethyl; R4 represents hydrogen, lower alkyl having one to four carbon atoms, benzyl, phenyl and phenethyl; and acid addition salts thereof with pharmaceutically acceptable acids.
 2. A compound selected from those of the formula wherein R3 represents hydrogen or lower alkyl of one to four carbon atoms; R4 represents hydrogen, lower alkyl of one to four carbon atoms, benzyl, phenyl and phenethyl; and acid addition salts thereof with pharmaceutically acceptable acids.
 3. 5,10-(Iminomethano)-5H-dibenzo(a,d)cyclohopten-11(10H)-one, as claimed in claim
 2. 4. The hydrochloric acid addition salt of 5,10-(iminomethano)-5H-dibenzo(a,d)cyclohepten-11(10H)-one, as claimed in claim
 2. 5. 13-Methyl-5,10-(iminomethano)-5H-dibenzo(a,d)cyclohepten-11(10H)-one, as claimed in claim
 2. 6. The Hydrochloric acid addition salt of 13-methyl-5,10-(iminomethano)-5H-dibenzo(a,d)cyclohepten-11(10H)-one, as claimed in claim
 2. 7. 13-Ethyl-5,10-(iminomethano)-5H-dibenzo(a,d)-cyclohepten-11(10H)-one, as claimed in claim
 2. 8. 13-Propyl-5,10-(iminomethano)-5H-dibenzo(a,d)cyclohepten-11(10H)-one, as claimed in claim
 2. 9. 13-Benzyl-5,10-(iminomethano)-5H-dibenzo(a,d)cyclohepten-11(10H)-one, as claimed in claim
 2. 10. 13-Phenethyl-5,10-(iminomethano)-5H-dibenzo(a,d)cyclohepten-11(10H)-one, as claimed in claim
 2. 11. 13-Phenyl-5,10-(iminomethano)-5H-dibenzo(a,d)cyclohepten-11(10H)-one, as claimed in claim
 2. 12. 12-Methyl-5,10-(iminomethano)-5H-dibenzo(a,d)cyclohepten-11(10H)-one, as claimed in claim
 2. 13. The oxalic acid addition salt of 12-methyl-5,10-(iminomethano)-5H-dibenzo(a,d)cyclohepten-11(10H)-one, as claimed in claim
 2. 14. A compound selected from those of the formula wherein R1 represents hydrogen and R1 represents hydroxyl, lower alkoxy having from one to three carbon atoms, dimethylamino, diethylamino, pyrrolidino, piperidino and morpholino; R3 represents hydrogen, lower alkyl having one to four carbon atoms, allyl, cyclopropylmethyl, benzyl, phenethyl, trimethoxybenzyl, dialkylaminoalkyl having from two to three carbon atoms in the alkyl radical and from one to three carbon atoms in each of the dialkyl radicals, pyrolidinoethyl, piperidinoethyl, 4''-methylpiperazinoethyl, 4''-phenylpiperazinoethyl and morpholinoethyl; and R4 represents hydrogen, lower alkyl having one to four carbon atoms, benzyl, phenethyl and phenyl; and acid addition salts thereof with pharmaceutically acceptable acids.
 15. A compound selected from those of the formula wherein R1 represents hydrogen, R2 represents hydroxyl, lower alkoxy having from one to three carbon atoms or pyrrolidino; R3 represents hydrogen or lower alkyl having one to four carbon atoms; and R4 represents hydrogen; and acid addition salts thereof with pharmaceutically acceptable acids.
 16. 10,11-Dihydro-11-methoxy-12-methyl-5,10-(iminomethano)-5H -dibenzo(a,d)cycloheptene, as claimed in claim
 15. 17. The hydrochloric acid addition salt of 10,11-dihydro-11-methoxy-12-methyl-5,10-(iminomethano)-5H-dibenzo (a, d)cycloheptene, as claimed in claim
 15. 18. 10,11-Dihydro-11-pyrrolidino-5,10-(iminomethano)-5H-dibenzo(a,d) -cycloheptene, as claimed in claim
 15. 19. 10,11-Dihydro-12-methyl-11-pyrrolidino-5,10-(iminomelhano)-5H -dibenzo(a,d)cycloheptene, as claimed in claim
 15. 20. 10,11-Dihydro-11-hydroxy-12-methyl-5,10-(iminomethano)-5H -dibenzo(a,d)cycloheptene, as claimed in claim
 15. 